A Dose-Finding Study of Birabresib (MK-8628), a Small Molecule Inhibitor of the Bromodomain and Extra-Terminal (BET) Proteins, in Adults With Selected Advanced Solid Tumors (MK-8628-003)

1. Signed informed consent obtained prior to initiation of any study-specific procedures and treatment;

2. Histologically or cytologically confirmed diagnosis of one of the following advanced or metastatic solid tumors for which standard therapy either does not exist or has proven ineffective, intolerable or inacceptable for the patient:

* NUT midline carcinoma (ectopic expression of NUT protein as determined by immunohistochemistry (IHC) and/or detection of BRD-NUT gene translocation as determined by fluorescence In situ hybridization \[FISH\]);

* Triple negative breast cancer defined according to American Society of Clinical Oncology (ASCO) recommendations (Hammond et al., 2010; Wolff et al., 2007);

* Non-small cell lung cancer harboring a rearranged ALK gene/fusion protein (FISH or IHC) or KRAS mutation (as defined by any molecular analysis);

* Castrate-resistant prostate cancer (CRPC);

* Pancreatic ductal adenocarcinoma;

3. At least one measurable lesion as per RECIST version 1.1., except for CRPC participants who may be enrolled with objective evidence of disease as per PCWG2 criteria;

4. Age ≥18 years at the time of informed consent;

5. Life expectancy ≥3 months;

6. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤1;

7. Adequate bone marrow reserve, renal and liver function:

* Absolute neutrophil count ≥1.5 x10\^9/L,

* Platelet count ≥150 x10\^9/L,

* Hemoglobin ≥9 g/dL,

* Creatinine clearance ≥30 mL/min calculated according to the Cockroft and Gault formula or Modification of Diet in Renal Disease (MDRD) formula for participants aged \>65 years,

* Alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤3 x upper limit of normal (ULN) and total bilirubin ≤1.25 x ULN (in case of liver involvement, ALT/AST ≤5 x ULN and total bilirubin ≤2 x ULN will be allowed),

* Serum albumin ≥2.8 g/dL,

* International Normalized Ratio (INR) ≤1.5 x ULN or INR \<3 for participants treated with antivitamin K;

8. An interval of ≥3 weeks since chemotherapy (≥6 weeks for nitrosoureas or mitomycin C), immunotherapy, hormone therapy or any other anticancer therapy or surgical intervention resection, or ≥3 half-lives for monoclonal antibodies, or ≥5 half-lives for other non-cytotoxic agents (whichever is longer);

9. CRPC participants must maintain ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) analogue, antagonist or orchiectomy providing serum testosterone is \<50 ng/dL (\<1.7 nmol/L);

10. Participants receiving bisphosphonate or denosumab therapy must be on stable doses for at least 4 weeks before initiating study treatment.

What this study is about